Knowing how DNA unwinds, copies and repairs itself—what starts it, what stops it and why—is vitally important to recombinant DNA research and will make possible major advancements in cancer treatment.

Piero
Bianco, PhD, is the first person to film a DNA motor protein
“unzipping” a double-strand of bacterial DNA.

Knowing how DNA unwinds, copies and repairs itself—what
starts it, what stops it and why—is vitally important to
recombinant DNA research and could make possible major advancements
in cancer treatment.

Developed Laser Tweezer Technique to Observe Repair

To make his movies, he uses a technique he developed called
“laser tweezers,” which he combines with fluorescence
microscopy and laminar flow cells to isolate individual molecules
of DNA and observe the action of the repair machinery in real
time.

Bianco developed his system while a postdoctoral fellow at the
University of California at Davis, in collaboration with
researchers from Lawrence Livermore National Laboratory.

The film features a molecule of Escherichia coli helicase,
called RecBCD, which acts by unzipping the DNA molecule from one
end to the other.

Since then, Bianco has made significant improvements to his filming
technique that have resulted in higher-resolution movies.

Films Depict Two Proteins Driving Recombination

Bianco also has adapted his system to investigate other, more
complex bacterial helicases, including RuvAB, a motor protein that
drives a critical late step in genetic recombination called branch
migration.

He is making a series of films that depict, for the first time,
how two key proteins work together in humans to drive recombination
and the exchange of genetic information.

The first, Rad54, is a motor protein. The second, Rad51, is a
type of enzyme known as a recombinase, which catalyzes the exchange
of strands of DNA between two DNA molecules, particularly in paired
maternal and paternal chromosomes.

Bianco has shown that when DNA is collapsed around the
recombinase, it makes it exponentially faster for Rad51 to locate
the correct spot on a strand needing repair.

Working to Assemble Full Recombination Reaction

Bianco’s work goes to the heart of one of the biggest
mysteries in recombinant DNA research: What biomechanical processes
are involved in invading a damaged strand of DNA and how to find
the repair target—a question that has enormous implications
for drug development.

He is now working toward his long-term goal: assembling an
entire recombination reaction.

Gabriela
Popescu, PhD, is studying NMDA receptors in the brain, which
are involved in synaptic development, plasticity, memory and
learning, as well as in pathologies such as stroke,
neurodegeneration, chronic pain, addiction, schizophrenia and
epilepsy.

Michael
Garrick, PhD, identified the first protein essential for normal
intestinal iron absorption and the first mammalian iron transporter
to be characterized at the molecular level. His work provides a
major step forward in the understanding of iron metabolism.

Daniel
Kosman, PhD, studies how organisms acquire and metabolize iron
and copper, intrinsically toxic metals essential to cellular
respiration and oxygen transport. One of his goals is to develop
antifungal drugs to treat infections in humans.

Thomas
Russo, MD, is internationally known for his work with strains
of E. coli that cause infections outside the intestine and result
in morbidity worldwide due to pneumonia, urinary tract infections
and meningitis.

Suzanne
Laychock, PhD, is investigating the cellular mechanisms
regulating insulin secretion in pancreatic cells. Her group has
used pancreatic cells in primary culture to develop in vitro
systems that mimic aspects of Type 1 and Type 2 diabetes.

Rajendram
Rajnarayanan, PhD, studies interactomes of the human estrogen
receptor, which is expressed in 70 percent of breast cancers. His
lab seeks to design molecules to improve the effects of
tamoxifen, a drug commonly prescribed to treat breast cancer.

Mulchand
Patel, PhD, is a specialist in nutritional biochemistry. He
found that fetuses of obese mother rats were programmed in utero to
develop obesity in adulthood, and was the first to show that this
metabolic programming occurs in the fetal hypothalamus.

James
R. Olson, PhD, has traveled to Egypt to work with cotton
laborers exposed to pesticides. His research links genetics, an
individual’s degree of exposure to pesticides and effects on
health, seeking to improve workplace and environmental health
worldwide.

Te-Chung
Lee, PhD, demonstrated for the first time, in an animal model,
that injecting adult bone marrow stem cells into skeletal muscle
can repair cardiac tissue, reversing heart failure. He and his team
showed that this non-invasive procedure increased heart cells
two-fold.